Effects of activation of mitochondrial aldehyde dehydrogenase 2 on MMP-14 and TIMP-4 in high glucose induced rat cardiomyocytes injury / 中国药理学通报

ABSTRACT

Aim To observe whether matrix metallo-proteinase-14 ( MMP-14) and tissue matrix metallopro-teinase inhibitor-4 ( TIMP-4) were involved in the car-diac-protection of mitochondrial aldehyde dehydrogen-ase 2 ( ALDH2) against high glucose induced rat pri-mary cardiomyocyte injury. Methods Rat primary cardiomyocytes were cultured. The cardiomyocyte via-bility was detected by MTT assay at different concentra-tion of glucose at different time point. After established high glucose-induced cardiomyocytes injury model, cardiomyocytes were randomly divided into 4 groups:normal control group ( NG, glucose at 5.5 mmol· L-1) , NG + Alda-1 group ( Alda-1 at 20 μmol·L-1) , high glucose group ( HG, glucose at 30 mmol·L-1) and HG+Alda-1 group. The cell viability at 48 h and oxidative stress level were detected by MTT and DHE staining methods. The protein expressions of ALDH2, MMP-14 and TIMP-4 were determined by Western blot. Results The cardiomyocytes injury model was established according to the cell activity result. Com-pared with NG group, the cell viability, the protein ex-pressions of ALDH2, MMP-14, the ratio of MMP-14/TIMP-4 were decreased, TIMP-4 protein expression and the level of oxidative stress were increased in HG group. Compared with HG group, in HG + Alda-1 group, the cell viability, the protein expressions of AL-DH2, MMP-14, the ratio of MMP-14/TIMP-4 were in-creased, the levels of oxidative stress and TIMP-4 pro-tein expression were decreased. Conclusion Activa-tion of mitochondrial ALDH2 may relieve high glucose induced cardiomyocytes injury. The protective effect was likely related to the inhibition of oxidative damage, down-regulation of MMP-14 and up-regulation of TIMP-4 proteins.